Study to Compare TP-434 and Ertapenem in CA Complicated Intra-abdominal Infections

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Tetraphase Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT01265784
First received: December 21, 2010
Last updated: July 5, 2012
Last verified: July 2012
  Purpose

This is a Phase 2, randomized, double-blind, double-dummy, multicenter, prospective study to assess the efficacy, safety, and pharmacokinetics of two dose regimens of TP-434 compared with ertapenem in the treatment of adult community-acquired complicated intra-abdominal infections.


Condition Intervention Phase
Complicated Intra-Abdominal Infection
Drug: TP-434
Drug: Ertapenem
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 2, Randomized, Double-Blind, Double-Dummy, Multicenter, Prospective Study to Assess the Efficacy, Safety, and PK of 2 Dose Regimens of TP-434 Compared With Ertapenem in Adult Community-Acquired Complicated Intra-abdominal Infections

Resource links provided by NLM:


Further study details as provided by Tetraphase Pharmaceuticals, Inc.:

Primary Outcome Measures:
  • Clinical response of TP-434 and ertapenem in the microbiologically evaluable population [ Time Frame: Test-of-Cure Visit (10-14 days after End-of-Treatment (EOT) visit) ] [ Designated as safety issue: No ]
    Clinical response of TP-434 and ertapenem in the treatment of hospitalized subjects with cIAI at the Test-of-Cure (TOC) visit.


Secondary Outcome Measures:
  • Clinical response of TP-434 and ertapenem [ Time Frame: EOT, TOC, and Follow-up (FU) Visits ] [ Designated as safety issue: No ]
    Determine clinical response in the following populations: 1) Modified intent-to-treat (MITT) population, 2) Clinically modified intent-to-treat (c-MITT) population, 3) Microbiologically modified intent-to-treat (m-MITT) population, 4) Clinically evaluable (CE) population, 5) Microbiologically evaluable (ME) population (EOT and FU)

  • Determine microbiologic response of TP-434 and ertapenem [ Time Frame: EOT, TOC ] [ Designated as safety issue: No ]
    To determine the microbiologic response at EOT and TOC visits in the following populations: 1) m-MITT population, 2) CE population, 3) ME population

  • Assess Safety and Tolerability of TP-434 (Adverse Events, Physical Exams, Vital Signs, ECGs, Lab Data) [ Time Frame: Screening, Days 1-14, EOT, TOC, FU ] [ Designated as safety issue: Yes ]
    Describe the safety profile of TP-434 in the MITT population

  • Explore the PK of TP-434 and ertapenem [ Time Frame: Day 1, Day 3, Day 5 ] [ Designated as safety issue: No ]
    Evaluate the Pharmacokinetics of TP-434


Enrollment: 143
Study Start Date: March 2011
Study Completion Date: May 2012
Primary Completion Date: May 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: TP-434, 1.5 mg/kg q24h
TP-434, 1.5 mg/kg q24h administered via IV infusion, plus saline placebo
Drug: TP-434
TP-434 reconstituted and administered via an IV infusion
Experimental: TP-434, 1.0 mg/kg q12h
TP-434, 1.0 mg/kg q12h administered via IV infusion, plus saline placebo
Drug: TP-434
TP-434 reconstituted and administered via an IV infusion
Active Comparator: Ertapenem 1 g q24h
Ertapenem, 1 g q24h administered via IV infusion, plus saline placebo
Drug: Ertapenem
Ertapenem reconstituted and administered via an IV infusion
Other Name: Invanz®

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Abdominal pain/discomfort with onset prior to hospitalization
  • Evidence of a systemic inflammatory response
  • Physical findings consistent with intra-abdominal infection (IAI)
  • Clinical diagnosis of community-acquired intra-abdominal infection requiring urgent surgical or percutaneous intervention and not expected to require antibacterial therapy for longer than 14 days
  • Body mass index (BMI) of ≤ 30 kg/m2
  • Able to provide informed consent. If the patient is unable to provide informed consent, the patient's legally acceptable representative may provide written consent in accordance with institutional guidelines
  • If female, not pregnant or nursing or, if of child-bearing potential either: will commit to use at least two medically accepted, effective methods of birth control (e.g., condom, oral contraceptive, indwelling intrauterine device, hormonal implant/patch, injections, approved cervical ring) during study drug dosing and for 90 days following last study drug dose or practicing sexual abstinence

Exclusion Criteria:

  • Symptoms related to diagnosis of complicated appendicitis (if current diagnosis) for < 24 hrs prior to current hospitalization
  • Previously hospitalized or admitted to a healthcare facility within the last 6 months
  • Managed by Staged Abdominal Repair or other open abdomen technique
  • Known at study entry to have an IAI caused by a pathogen(s) resistant to both study drug antibiotics
  • APACHE II score > 25
  • Unlikely to survive the 6-8 week study period
  • Any rapidly-progressing disease or immediately life-threatening illness, including acute hepatic failure, respiratory failure and septic shock
  • Requirement for vasopressors at therapeutic dosages
  • Renal failure
  • Presence or possible signs of hepatic disease
  • Hematocrit < 25% or hemoglobin < 8 g/dL
  • Neutropenia with absolute neutrophil count < 1000/mm3
  • Platelet count < 50,000/mm3
  • Abnormal coagulation tests or patient on anticoagulants
  • Immunocompromised condition, including known HIV positivity or AIDS, organ (bone marrow) transplant recipients, and hematological malignancy. Immunosuppressive therapy, including use of high-dose corticosteroids (e.g., > 40 mg prednisone or equivalent per day for greater than 2 weeks)
  • History of hypersensitivity reactions to tetracyclines or carbapenems
  • Participation in any investigational drug or device study within 30 days prior to study entry
  • Known or suspected central nervous system (CNS) disorder that may predispose to seizures or lower seizure threshold
  • Previously received TP-434 in a clinical trial
  • More than 24 hrs duration of systemic antibiotic coverage for current condition or received ertapenem or any other carbapenem, or tigecycline for the current infection or
  • Need for concomitant systemic antimicrobial agents other than study drug or received systemic (IV or oral) antibiotics in the last 3 months
  • Refusal of mechanical ventilation, dialysis or hemofiltration, cardioversion or any other resuscitative measures and drug/fluid therapy at time of consent
  • Known or suspected inflammatory bowel disease or associated visceral abscess
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01265784

  Show 38 Study Locations
Sponsors and Collaborators
Tetraphase Pharmaceuticals, Inc.
Investigators
Study Director: Patrick T Horn, MD, PhD Tetraphase Pharmaceuticals, Inc.
  More Information

No publications provided

Responsible Party: Tetraphase Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT01265784     History of Changes
Other Study ID Numbers: TP-434-P2-cIAI-1
Study First Received: December 21, 2010
Last Updated: July 5, 2012
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Additional relevant MeSH terms:
Ertapenem
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 23, 2014